Original Article

Journal of the
ASEAN Federation of
Endocrine Societies

Congenital Hypothyroidism in Children –

A Cross-Sectional Study in a Tertiary Centre in Malaysia*
Azriyanti Anuar Zaini,1 Yu Feng Tung,1 Nor Faizal Ahmad Bahuri,2 Muhammad Yazid Jalaludin1
1
Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
2
Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Abstract

Introduction. The causes of congenital hypothyroidism (CHT) are thyroid dysgenesis (TD), dyshormonogenesis (TDH) or
transient hypothyroidism (TH).

Methodology. This is a cross-sectional study looking at data over a period of 16 years (2000-2016). Confirmed cases had
thyroid scan at the age of 3-years-old and repeated TFT (after 6 weeks off medications). Relevant data was collected
retrospectively.

Results. Forty (60% female) children with CHT were included in the study. Thirty (75%) children presented with high cord
TSH. Nine (23%) presented after 2 weeks of life. Majority were diagnosed with TDH (42.5%) with TD and TH of 40% and
17.5% respectively. Median cord TSH of children with TD was significantly higher compared to TDH and TH (p=0.028
and p=0.001 respectively). L-thyroxine doses were not significantly different between TD, TDH and TH at diagnosis
or at 3 years.

Conclusions. TDH is highly prevalent in our population. TD may present after 2 weeks of life. One in five children
treated for CHT had TH. Differentiating TD, TDH and TH before initiating treatment remains a challenge in Malaysia.
This study provides clinicians practical information needed to understand the possible aetiologies from a patient’s
clinical presentation, biochemical markers and treatment regime. Reassessing TH cases may be warranted to prevent
unnecessary treatment.

Key words: congenital hypothyroid, thyroid dysgenesis, thyroid dyshormonogenesis, transient hypothyroid, thyroxine,
cord blood TSH

INTRODUCTION hypothyroidism, which can be due to maternal thyroid

disease, prematurity or iodine deficiency. These children
Thyroid hormone is vital for the normal functioning of are usually on temporary thyroxine replacement.
various organs in the body, including neural growth
and transmission. This is especially important as studies The prevalence of congenital hypothyroidism worldwide
have shown that there is a close association of thyroid is around 1 in 4000 livebirths in USA, Canada and Western
hormone with foetal brain development.1 Congenital hypo- Europe.4 In our neighbouring country, Singapore,5 the
thyroidism (CHT) is the term used when the production prevalence was reported as 1 in 3000 live births. Local
of the thyroid hormones are inadequate or deficient in studies in Malaysia have reported the prevalence of
newborn babies. It is an important diagnosis to be made CHT as between 1600 to 3500 per 100,000 live births.6,7
early to prevent mental retardation in children. Cord blood The prevalence of CHT in University Malaya Medical
or early serum TSH screening has been widely used to Centre (UMMC) was reported as 1 in 1515 term babies,
detect CHT.2-3 slightly higher than previously reported Malaysian data.7

Permanent or true congenital hypothyroidism is Data obtained from Leicester Royal Infirmary in UK,8
divided into thyroid dysgenesis (agenesis or ectopics) reported that congenital hypothyroidism is more
(TD) or thyroid dyshormonogenesis (TDH). Children prevalent in Asians compared to non-Asians, with the
with permanent congenital hypothyroidism require affected population of children mostly had thyroid
lifelong thyroxine replacement. There is an increasing dysgenesis (1 in 4000). Another study from the University
recognition of transient hypothyroidism or subclinical of Montreal, Canada,9 found that for thyroid dysgenesis,
________________________________________

ISSN 0857-1074 (Print) | eISSN 2308-118x (Online) Corresponding author: Azriyanti Anuar Zaini, MBBS, MPaeds
Printed in the Philippines Consultant Paediatric Endocrinologist
Copyright © 2020 by Zaini et al. Department of Paediatrics, Faculty of Medicine, University of Malaya
Received: November 16, 2019. Accepted: February 5, 2020. 50603 Kuala Lumpur Malaysia
Published online first: April 21, 2020. Tel. No.: +6037949 3909/6468
https://doi.org/10.15605/jafes.035.01.11 Fax No.:+6037949 4722
E-mail: [email protected]
ORCiD: 0000-0001-5659-765X

* Presented as oral presentation at the Malaysian Endocrine and Metabolic Society (MEMS) Annual Conference 7, 20-22 May 2016, Kuala Lumpur Malaysia –
won best oral presentation.

62 www.asean-endocrinejournal.org Vol. 35 No. 1 May 2020

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
Congenital Hypothyroidism in Children – A Cross-Sectional Study in a Tertiary Centre in Malaysia Azriyanti Anuar Zaini, et al 63

females were more affected compared to males. In Yazd, This study aims to guide clinicians in developing countries
Central Iran,10 a larger population (54.5%) of children with limited resources to understand the aetiologies and
with transient hypothyroidism was reported compared possible outcome based on patients’ clinical presentation.
to permanent hypothyroidism. However, the study This includes timing of presentation, biochemical
population was small with only 22 children. In Malaysia, markers and treatment regimes.
there is inadequate data to suggest distribution, however,
a short report in 2009 showed thyroid dyshormono- METHODOLOGY
genesis was much more prevalent than thyroid
dysgenesis.7.11 A cross-sectional study was conducted looking at data
over 16 years from 2000-2016. This is to determine the
Initial presentation of children with CHT can be variable, prevalence, demographic profile, clinical and biochemical
with most being asymptomatic if detected early. Other parameters of all CHT patients on follow-up at UMMC
symptoms include sleepiness, poor feeding, cold Paediatric Endocrinology clinic. UMMC is a tertiary referral
extremities, prolonged neonatal jaundice, lethargy, centre in the urban population of Kuala Lumpur. Our study
hypotonia, macroglossia, umbilical hernia, coarse population were term babies born between year 2000 to
facies and dry skin. Delayed bone maturation is shown year 2013 without any congenital anomaly or suspected
through delayed closure of posterior fontanelle, large syndrome. We identified CHT cases based on 3 sub-group
anterior fontanelle and wide sagittal suture. CHT if not diagnosis namely thyroid dysgenesis, dyshormonogenesis
treated will cause significant reduction in irreversible, and transient hypothyroidism. These cases must have
permanent nervous system damage and a consequent complete confirmatory diagnostic tests (re-testing TFT and
developmental delay. Previous studies have shown that thyroid scan) which was performed at 3 years old. We then
the first 4 to 6 weeks of life is a phase crucial for postnatal collected data retrospectively from each case for analysis.
brain development and a delay in treatment for one week All subjects were anonymised and potential identifiers
can cause a significant reduction of IQ (approximately 10 removed. Relevant data was tabulated and analysed
points) in children with CHT.12 This is why early detection using SPSS software 22.0. This study was approved by the
and early treatment is so important. Meanwhile a study hospital ethics committee MREC No 2018913-6676.
conducted by Albert BB et al., in New Zealand13 has
shown that children with CHT even when treated early Early presentation is defined as a patient presenting
had delayed normalisation of the T4 values that may affect with either high cord blood TSH at screening or with
the child’s motor balance. This suggests the importance of symptoms before 2 weeks of life and late if presented after
early and aggressive treatment in this group of patients. 2 weeks of life.

The Malaysian National CHT screening programme STATISTICS

was initiated in October 1998. TSH levels are taken from
cord blood due to logistics purposes.14 Babies with cord Period prevalence was calculated based on the centre’s
blood TSH more than 40 mIU/L is highly suspicious for livebirth registry and confirmed CHT cases. Kruskal-Wallis
CHT. Cord blood TSH between 20-40 mIU/L will also be test was performed to compare the three types of CHT
recalled for a repeat test. Serum fT4 and TSH between day and post hoc analysis was done to explore the differences.
3 and 5 would be done for confirmation. Abnormal TFT Fishers exact test for gender and ethnicity was also
performed between day 3 and 5 are treated according to performed to reflect association between the groups.
AAP 2006 guidelines.15 Those born prior to 2006 were
treated according to AAP guidelines 1993.16 Babies with RESULTS
normal cord blood TSH but later found to have abnormal
TFT levels (TSH >10 mIU/L with a relatively lower fT4 Total number of livebirth from 2000-2013 was 72,652 in
levels <15 pmol/L) were treated. this centre. A total of 223 cases were suspected to have
CHT. Only 40 cases met the inclusion criteria and were
In developed countries, thyroid scans are done shortly after included in the analysis. These cases were confirmed to
positive initial screening. However, in Malaysia, due to the have congenital hypothyroidism (CHT). The calculated
limited availability of thyroid scans, babies suspected to period prevalence in this study group is 0.055%. The most
have CHT were not subjected to thyroid scan at initiation common type of CHT seen is thyroid dyshormonogenesis
of treatment, compared to some other centres in the world. (n=17,42.5%), followed by thyroid dysgenesis (n=16,40%)
Instead the scan is done at age 3 years. Babies who were and transient hypothyroidism (n=7,17.5%). Despite being
started on treatment would have their levels monitored the least common, about 1 out of 5 children with CHT had
monthly for the first 6 months, then every 2 to 3 months transient hypothyroidism and were treated with thyroxine
until 2 years old and subsequently every 3 to 4 months for at least 3 years.
until the age of 3 years. At that point, treatment would be
stopped for 4-6 weeks before the children were sent for Demographics
thyroid scan. TFT would also be taken just prior to the We have found that CHT in our population has a female
thyroid scan. Thyroid dysgenesis (TD) is diagnosed if the preponderance (60% p=0.019) (Table 1). This is especially
child has both abnormal thyroid scan and TFT at 3 years true with thyroid dysgenesis (81.3% female) and transient
old. Children with abnormal TFT but have normal thyroid hypothyroidism sub-groups (71.4% female) (Table 1).
scan are considered to have thyroid dyshormonogenesis Apart from gender, ethnicity difference was equally
(TDH). Transient hypothyroidism (TH) children will significant across 3 major ethnicity group in Malaysia
have normal scan and normal TFT. Only those with TD or (p=0.027). Chinese ethnicity was the majority in this
TDH will eventually need thyroxine for life. population (47.5%). However, comparing sub-groups, 50%

Vol. 35 No. 1 May 2020 www.asean-endocrinejournal.org

64 Azriyanti Anuar Zaini, et al Congenital Hypothyroidism in Children – A Cross-Sectional Study in a Tertiary Centre in Malaysia

Table 1. The distribution by gender in different types of hernia, skin mottling, feeding difficulty and absent of
congenital hypothyroidism femoral epiphyses). All late presenters from thyroid
Types of CHT Male Female Total dyshormonogenesis group presented with mild symptoms
TD 3 (18.8%) 13 (81.3%) 16 of prolonged jaundice. It was more common for cases with
TDH 11 (64.7%) 6 (35.3%) 17 transient hypothyroidism to present later with delayed
TH 2 (28.6%) 5 (71.4%) 7 TSH rise. Most were asymptomatic. One was incidentally
Total 16 24 40 found to have abnormal T4 levels during extensive
p=0.019 *Fisher’s Exact test workout for hypotonia and poor weight gain. She was
treated with thyroxine when her T4 was persistently low
of the children who had thyroid dysgenesis were Malays, (<15 pmol/L) despite normal TSH (6.33 mIU/L) (Table 3.1).
70.6% of children with thyroid dyshormonogenesis were
Chinese and 42.9% of those with transient hypothyroidism Biochemical levels
were Indians (Table 2). Median cord blood TSH level was observed to be higher in
children with thyroid dysgenesis and dyshormonogenesis
Table 2. The distribution by ethnicity in different types of as compared to those with transient hypothyroidism. There
congenital hypothyroidism was significant difference between the cord blood TSH
Types of CHT Malay Chinese Indian Total level when compared to all sub-groups (p=0.01) (Table 4).
TD 8 (50%) 5 (31.3%) 3 (18.7%) 16
TDH 5 (29.4%) 12 (70.6%) 0 (0%) 17 Post hoc analysis confirms statistically significant
TH 2 (28.6%) 2 (28.6%) 3 (42.9%) 7 difference between levels in thyroid dysgenesis and
Total 15 19 6 40 thyroid dyshormonogenesis (p=0.028) and when compared
p=0.027 *Fisher’s Exact test
between thyroid dysgenesis and transient hypothyroidism
(p=0.001) (Table 4.1).
Timing of presentation
Among all the children with CHT (n=40), 31 (77.5%) Dosing and treatment
of them presented early with high cord blood TSH or At initiation of treatment, the mean starting dose
abnormal TSH above 10 mIU/L within first 2 weeks of life. of L-Thyroxine for thyroid dysgenesis, thyroid
The remaining 9 (22.5%) presented at or more than 2 weeks dyshormonogenesis and transient hypothyroidism
of life. Only 1 in 8 children with thyroid dysgenesis and were 11.83±3.88, 8.84±3.83 and 6.34±1.97 mcg/kg/day
thyroid dyshormonogenesis presented late. Majority of respectively. Although it appears to be different, Kruskal-
children (57%) with transient hypothyroidism presented Wallis test showed no significant difference between the
late (Table 3). three groups (p=0.614).

Table 3. Timing of presentation Similarly at 3 years old, there were no statistical difference
CHT Within first 2 weeks of More than 2 weeks of
Total between the doses taken by the children comparing
number
Type life (Early Presentation) life (Late Presentation) all groups (p=0.056). The mean L-thyroxine dose were
of cases
TD 14 (87.5%) 2 (12.5%) 16
3.18±0.69, 2.56±0.79 and 1.91±0.82 mcg/kg/day for thyroid
TDH 14 (82.4%) 3 (17.6%) 17 dysgenesis, thyroid dyshormonogenesis and transient
TH 3 (42.8%) 4 (57.2%) 7 hypothyroidism respectively (Table 5).
Total 31 (77.5%) 9 (22.5%) 40
DISCUSSION

Clinical presentation The maturation process of the brain in a child requires

Clinically, children who presented early (n=31) were thyroid hormone.17 The significant role that thyroid
asymptomatic regardless of the type of CHT. Two cases hormone plays in brain development is undeniable, at
of thyroid dysgenesis presented late. One had a missing which the deficiency of it would then cause cretinism.
record of cord blood TSH, however despite reminder, Fortunately, this form of mental retardation can be
parents did not turn up for a repeat test and returned to avoided18 if hypothyroidism is detected and treated
their rural hometown for confinement. The second case early. Thus, neonatal screening is crucial because early
had normal cord blood TSH. Both presented at much detection and treatment of congenital hypothyroidism can
later stages with profound hypothyroidism (umbilical prevent mental retardation. In addition, early detection

Table 3.1. Case demographics of late presenters

Cases Age presented to UMMC Gender Clinical presentation Cord TSH (miu/L) Diagnosis
1 4 weeks Girl Macroglossia, umbilical hernia, hypotonia, constipation Missed, No follow- up TD
2 5 months Girl Macroglossia, umbilical hernia, hypotonia, constipation, 8.0 TD
goitre, absent of tibia epiphysis on bone radiography
3 3 – 4 weeks Girl Prolonged jaundice 12.0 TDH
4 3 – 4 weeks Girl Prolonged jaundice 6.0 TDH
5 3 – 4 weeks Boy Prolonged jaundice 4.0 TDH
6 >2 weeks (6 weeks old) Boy Delayed TSH rise 7.0 TH
7 2 weeks of life Girl Delayed TSH rise 7.0 TH
8 >2 weeks (9 months old) Girl Hypotonia, poor weight gain, low T4, normal TSH 21.0 TH
9 >2 weeks (3 weeks old) Boy Delayed TSH rise 5.0 TH

www.asean-endocrinejournal.org Vol. 35 No. 1 May 2020

Congenital Hypothyroidism in Children – A Cross-Sectional Study in a Tertiary Centre in Malaysia Azriyanti Anuar Zaini, et al 65

Table 4. Median cord TSH values of different subgroups also showed a significantly higher incidence of congenital
of CHT hypothyroidism in Asian families--1/918 compared
TD TH TDH with 1/3391 in non-Asians.21 A study from the UK22 also
CHT Type p-value
(n=16) (n=7) (n=17) showed predominance in Asian families to have CHT
Median Cord TSH (miu/L) 109.80 21.30 28.64 0.01* and females are more affected than males. In our study,
Maximum level (miu/L) 595.00 28.00 167.00 the majority (42.5%) of our children with CHT had
Minimum level (miu/L) 8.00 5.00 4.00 thyroid dyshormonogenesis. This is followed by thyroid
*p-value calculated using Kruskal-Wallis test
dysgenesis (40%) and the remaining 17.5% transient
hypothyroidism. We have demonstrated the ethnicity
Table 4.1. Post Hoc analysis predisposition for CHT. This result also supports a paper
Comparison p-value published on New Zealand Asian births which had higher
Transient (TH) – Dyshormonogenesis (TDH) 0.337 rates of dyshormonogenesis compared to New Zealand
Transient (TH) – Dysenesis (TD) 0.001* Europeans23 and consolidates our previous report where
Dyshormonogenesis (TDH) – Dysgenesis (TD) 0.028* we found that the majority of our patients with congenital
*p-value calculated using Kruskal-Wallis test hypothyroidism are thyroid dyshormonogenesis.11

Table 5. Mean dosage (initial dose and last dose) of Malaysia has a total population of 32.6 million, the
L-Thyroxine/day in children with thyroid dysgenesis majority are Malays (69%, followed by Chinese (22.8%)
(TD), thyroid dyshormonogenesis (TDH) and transient and Indians (6.9%).24 We found that distribution of CHT
hypothyroidism (TH) in our centre affects more Chinese (47.5%), followed
Last dose thyroxine by Malays (37.5%) and the Indians (15%). The Chinese
Starting thyroxine
Types at 3-years-old population were found to be more predisposed to have
of CHT
Early Late
On Not on thyroid dyshormonogenesis (70.6%), while the Malays
treatment treatment (50%) had thyroid dysgenesis and Indian population tend
TD 15 1 16 0
to have transient hypothyroidism. This report supports
n=16(40%) (94%) (6%) (100%)
Mean dose
another study by Lee et al., who reported 4 Malaysian-
11.8 ± 3.88 3.18 ± 0.69 Chinese children with thyroid mutation genes (c.2268dup)
(mcg/kg/day)
TDH 11 6 17 0 related to thyroid dyshormonogenesis.25 Lee et al. also
n=17(42.5%) (64%) (36%) (100%) describes similar findings in 2 siblings with CHT who
Mean dose presented with goitre during late teenage years.26 Studies
8.84 ± 3.83 2.56 ± 0.79
(mcg/kg/day)
from California also showed increase prevalence of CHT in
TH 2 5 6 1
n=7(17.5%) (28%) (72%) (86%) (14%) certain Chinese and Asian Indian ethnic groups.27
Mean dose
6.38 ± 1.97 1.91 ± 0.82
(mcg/kg/day) One would anticipate a child with thyroid dysgenesis
**p=0.614 **p=0.056 would not be able to produce thyroxine hence the high
levels of cord TSH. We report 2 cases (12.5%) who presented
late with profound symptoms. One child had no record of
also ensures better developmental outcomes through cord TSH. This was a missed case (inadequate cord blood
early thyroid hormone replacement in children with sampling). Unfortunately, due to logistics issue, parents
congenital hypothyroidism. did not return child for a repeat sample at D3-5 despite
reminder. This child presented with profound symptoms
University Malaya Medical Centre (UMMC) has at 4 weeks old. The other child had a normal cord TSH
been practicing neonatal screening for congenital which was unexpected. She presented much later with
hypothyroidism using cord blood TSH since the late profound symptoms. Hypopituitarism was excluded. This
1980’s. Further confirmation by serum TFT would be ‘normal’ cord TSH could have been a diluted sample or
then carried out on day 3 to 5 of life, at which treatment is contaminated with maternal blood.
instituted if the diagnosis was made. At the age of 3 years,
all children treated for CHT were subjected to thyroid scan In thyroid dyshormonogenesis, the gland is normally
to confirm the cause of CHT. From diagnosis to 3 years formed but its function is abnormal, resulting in inadequate
old, these children were monitored closely and dosage T4 and T3 levels, inducing an increase in TSH levels.
adjustment was done according to laboratory tests, the Depending on the severity, cord TSH may not be as high
TSH and fT4 levels. and abnormal as thyroid dysgenesis. Some may have
either normal or borderline raised levels and these children
We report significant proportion in relation to gender. may present later with milder symptoms. In this study,
More females were found to have CHT (thyroid dysgenesis we report 3 cases (17%) who presented with prolonged
and transient hypothyroidism) in our population. However, jaundice and had normal cord TSH with delayed TSH rise.
for thyroid dyshormonogenesis, boys predominate.
Although not widely reported, this trend was also seen Majority of the children with transient hypothyroidism
in few research studies published on the demographics of had delayed rise in TSH levels and their cord TSH are well
population of children with congenital hypothyroidism, within the normal range. These babies were recalled every
where female to male ratio is 2:1.4, 15, 19 1-2 weeks to monitor their TSH levels. If the TSH remains
abnormal according to AAP 2006 guidelines, we started
In previous studies, Asians are shown to have much them on low dose thyroxine replacement to prevent further
higher incidence of thyroid dyshormonogenesis.20 rise in TSH levels. Three out of four late presenters were
Screening in the North West health region of England asymptomatic. The child who presented with hypotonia

Vol. 35 No. 1 May 2020 www.asean-endocrinejournal.org

66 Azriyanti Anuar Zaini, et al Congenital Hypothyroidism in Children – A Cross-Sectional Study in a Tertiary Centre in Malaysia

and poor weight gain was extensively investigated and trends were performed regularly. None had a trial of
was found to have persistently abnormal T4 levels between stopping thyroxine despite using lower doses due to fear
the age of 8-9 months. The cause of hypothyroidism of potential neurocognitive impairment.
was not identified.
The next question is whether stopping treatment
There are a few possibilities to the causes of transient earlier for children whom we suspect have transient
hypothyroidism.28 Iodine deficiency is a condition hypothyroidism can be safely done. From this report,
to consider. Malaysian population is at high risk of we do know that they usually present later, are mostly
iodine deficiency. Nazaimoon et al., has shown that up asymptomatic, and required relatively lower doses. JCEM
to 49% of children between 8-10 years old are iodine 2014 guidelines suggests re-evaluation after stopping
deficient.29 Another report from Sabah showed that iodine thyroxine preferably after 3 years of life, however earlier
deficiency among pregnant and breastfeeding mothers in retesting may be possible in cases suspected with transient
Malaysia is high.30 This is surprising as Sabah is known hypothyroidism. Bloods should be repeated after 2 weeks
to have sufficient supply of seafood sources throughout of stopping and monitored regularly.34
different levels of society.
We would suggest clinicians, especially general
In Kuala Lumpur, although the hospital is situated in an paediatricians in Malaysia, to consider titrating further
urban location, the mean monthly household income is and stop thyroxine earlier (before 3 years old) in children
approximately RM 5000 (equivalent to USD 1200),31 fish and suspected with transient hypothyroidism. This should
seafood can be expensive and unaffordable to many. More be done under proper monitoring and guidance of an
local studies and data are needed to measure iodine levels experienced paediatric endocrinologist.
in babies and their mothers especially the ones presenting
later or with subclinical hypothyroidism. Other reasons CONCLUSION
included maternal thyroid disease or postnatal exposure
to iodine (in our cases none had these) or maternal TRabs The most common type of CHT seen were thyroid
(We did not investigate this further). dyshormonogenesis followed by thyroid dysgenesis
and transient hypothyroidism. Children with thyroid
When comparing cord blood TSH levels between the dysgenesis may present after 2 weeks of life. One in
3 sub-groups, we found that the median cord TSH in 5 children who were treated for CHT had transient
children with thyroid dysgenesis is expectedly higher hypothyroidism. Given that the prevalence of transient
than the children with thyroid dyshormonogenesis and hypothyroidism is common, clinicians may consider
transient hypothyroidism. However, between thyroid withholding or tapering off thyroxine earlier than 3 years
dyshormonogenesis and transient hypothyroidism, there old with careful assessment and diligent monitoring.
is no significant difference in the median cord TSH level.
This data suggests that as clinicians, although one can This study provides clinicians with practical information
easily suspect a case with thyroid dysgenesis, one should to understand the possible aetiologies of CHT from a
not assume or predict the diagnosis without proper patient’s clinical presentation, biochemical markers and
diagnostic testing. In our centre and in Malaysia generally, treatment regime. Although genetic mutations for thyroid
the diagnostic test can only be done at the age of 2-3 years dysgenesis and dyshormonogenesis are available in some
old after stopping thyroxine for 4-6 weeks. centres worldwide, funding and opportunity may not be
sufficient for most centres in Malaysia to proceed with
At diagnosis, children with thyroid dysgenesis and genetic diagnosis.
dyshormonogenesis were relatively given higher doses
as compared to children with transient hypothyroidism. Statement of Authorship
We used the recommended guidelines of 10-15 mcg/ All authors certified fulfillment of ICMJE authorship criteria.
kg at diagnosis and adjustment was made according
to biochemical levels.15,32 Children with transient Author Disclosure
The authors declare no conflict of interest.
hypothyroidism were given a lower dose, which was found
to be adequate enough to suppress their mildly elevated Funding Source
TSH. However, there was no statistical difference in the None.
median thyroxine doses for the different 3 sub-groups. This
suggests that clinicians are following general guidelines References
of treating CHT regardless of cord blood TSH levels. 1. Chan S, Kilby MD. Thyroid hormone and central nervous system
Further analysis on the titration of dosages and timing development. J Endocrinol. 2000;165(1):1-8. PMID: 10750030. https://
doi.org/10.1677/joe.0.1650001.
for TSH to normalise may give more insight to clinician to 2. Henry G, Sobki SH, Othman JM. Screening for congenital
suspect the severe cases of CHT. Mathai et al., from New hypothyroidism. Saudi Med J. 2002;23(5):529-35. PMID: 12070574.
Zealand reported the variability and pattern, however the 3. Buyukgebiz A. Newborn screening for congenital hypothyroidism.
J Clin Res Pediatr Endocrinol. 2013;5(Suppl 1):8-12. PMID: 23154158.
aetiologies were different from our population.33 PMCID: PMC3608007. https://doi/org/10.4274/jcrpe.845.
4. Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J
By the time these children were 3 years old, children Rare Dis, 2010. 5:17. PMID: 20537182. PMCID: PMC2903524. https://
doi.org/10.1186/1750-1172-5-17.
with dysgenesis and dyshormonogenesis remained on
5. Joseph R. Mass newborn screening in Singapore. Southeast Asian J
slightly higher dose as compared to those with transient Trop Med Public Health. 2003;34(Suppl 3):89-90. PMID: 15906706.
hypothyroidism. However, our data was not significant 6. Zarina AL, Rahman R, Bador KM, Ng SF, Wu LL. Audit of newborn
enough to suggest that children on lower doses would screening programme for congenital hypothyroidism. Med J
Malaysia. 2008;63(4):325-8. PMID: 19385494.
likely be transient. Titrating doses according to TSH

www.asean-endocrinejournal.org Vol. 35 No. 1 May 2020

Congenital Hypothyroidism in Children – A Cross-Sectional Study in a Tertiary Centre in Malaysia Azriyanti Anuar Zaini, et al 67

7. Wong SLW, Jalaludin M, Anuar A, Samingan N, Harun F. Congenital 23. Albert BB, Cutfield WS, Webster D, et al. Etiology of increasing
hypothyroidism: An audit and study of different cord blood screening incidence of congenital hypothyroidism in New Zealand from 1993–
tsh values in a tertiary medical centre in Malaysia. Advances in 2010. J Clin Endocrinol Metab. 2012;97(9):3155-60. PMID: 22723332.
Endocrinology. 2015;2015. https://doi.org/10.1155/2015/387684. https://doi.org/10.1210/jc.2012-1562.
8. Kapoor S, Kapoor D, Kapoor VK Congenital hypothyroidism: 24. Current population estimates, Malaysia 2018-2019. Department
Its profile in infancy. Thyroid Res Pract. 2013;10(3):47-55. https:// of Statistics, Official Portal. Available at https://www.dosm.
doi.org/10.4103/0973-0354.110577. gov.my/v1/index.php?r=column/cthemeByCat&cat=155&bul_
9. Euge`ne D, Djemli A, Van Vliet G. Sexual dimorphism of thyroid id=aWJZRkJ4UEdKcUZpT2tVT090Snpydz09&menu_
function in newborns with congenital hypothyroidism. J Clin id=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09.
Endocrinol Metab. 2005;90(5):2696–700. PMID: 15728201. https:// 25. Lee CC, Harun F, Jalaludin MY, Heh CH, Othman R, Junit SM.
doi.org/10.1210/jc.2004-2320. Prevalence of c. 2268dup and detection of two novel alterations, c.
10. Ordooei M, Rabiei A, Soleimanizad R, Fatemeh M. Prevalence of 670_672del and c. 1186C> T, in the TPO gene in a cohort of Malaysian–
permanent congenital hypothyroidism in children in Yazd, Central Chinese with thyroid dyshormonogenesis. BMJ Open. 2015;5(1):
Iran. Iran J Public Health, 2013;42(9):1016-20. http://ijph.tums.ac.ir. p. e006121. PMID: 25564141. PMCID: PMC4289740. https://doi.
11. Azriyanti AZ, Yazid MJ, Fatimah H, Thyroid gland phenotype org/10.1136/bmjopen-2014-006121.
in primary congenital hypothyroidism. Hormone Research. 26. Lee CC, Harun F, Jalaudin MY, Lin CY, Ng KL, Junit SM. Functional
2008;70(Suppl 3):58. analyses of c.2268dup in thyroid peroxidase gene associated with
12. Rovet JF. Congenital hypothyroidism: Long-term outcome. goitrous congenital hypothyroidism. Biomed Res Int. 2014;2014:
Thyroid.1999;9(7):741-8. PMID: 10447023. https://doi.org/10.1089/ Article ID 370538. https://doi.org/10.1155/2014/370538.
thy.1999.9.741. 27. Waller DK, Anderson JL, Lorey F, Cunningham GC. Risk factors
13. Albert BB, Heather N, Derraik JG, et al., Neurodevelopmental and body for congenital hypothyroidism: An investigation of infant's birth
composition outcomes in children with congenital hypothyroidism weight, ethnicity, and gender in California, 1990–1998. Teratology.
treated with high-dose initial replacement and close monitoring. 2000;62(1):36-41. PMID: 10861631. https://doi.org/10.1002/1096-
J Clin Endocrinol Metab. 2013;98(9):3663-70. PMID: 23861458. https:// 9926(200007)62:1<36::AID-TERA8>3.0.CO;2-W.
doi.org/10.1210/jc.2013-1903. 28. Parks JS, Lin M, Grosse SG, et al. The impact of transient
14. Harun F, Ch'ng SL. Congenital hypothyroidism in a developing hypothyroidism on the increasing rate of congenital hypothyroidism
country. Proceedings of Clinical Thyroidology Meeting. Innsbruck, in the United States. Pediatrics. 2010;125(Suppl 2): S54-63. PMID:
Austria; 1992. 20435718. https://doi.org/10.1542/peds.2009-1975F.
15. American Academy of Pediatrics, Rose SR, Section on Endocrinology 29. Selamat R, Mohamud WN, Zainuddin AA, Rahim NS, Ghaffar SA, Aris
and Committee on Genertics, et al. Update of newborn screening T. Iodine deficiency status and iodised salt consumption in Malaysia:
and therapy for congenital hypothyroidism. Pediatrics. 2006;117(6): Findings from a national iodine deficiency disorders survey. Asia Pac
2290-303. PMID: 16740880. https://doi.org/10.1542/peds.2006-0915. J Clin Nutrition. 2010;19(4):578-85. PMID: 21147721.
16. Americn Academy of Pediatrics AAP Section on Endocrinology and 30. Lim KK, Chan YY, Teh CH, et al. Iodine status among pregnant
Committtee on Genetics, and American Thyroid Association Committee women in rural Sabah, Malaysia. Asia Pac J Clin Nutr. 2017;26(5):861-
on Public Health: Newborn screening for congenital hypothyroidism: 6. PMID: 28802296. https://doi.org/10.6133/apjcn.092016.06.
Recommended guidelines. Pediatrics. 1993;91(6):1203-9. PMID: 31. Report of household income and basic amenities survey 2016. Department
8502532. of Statistics Malaysia, Official Portal. Available at https://www.
17. Bernal J. Thyroid hormones in brain development and function.: South dosm.gov.my/v1/index.php?r=column/cthemeByCat&cat=120&bul_
Dartmouth (MA): MDText.com, Inc; Updated 2015. https://www.ncbi. i d = R U Z 5 R E w v e U 1 r a 1 h G L 2 1 J W Vl P R m U 2 Z z 0 9 & m e n u _
nlm.nih.gov/books/NBK285549/. id=amVoWU54UTl0a21NWmdhMjFMMWcyZz09.
18. Dunn JT. Iodine supplementation and the prevention of cretinism. 32. Schoelwer MJ, Tu W, Zhou J, Eugster EA. Targeted levothyroxine
Ann N Y Acad Sci. 1993;678:158-68. PMID: 8494259. https://doi. therapy for treatment of congenital hypothyroidism. Endocr Pract.
org/10.1111/j.1749-6632.1993.tb26119.x. 2017;23(9):1067-71. PMID: 28683242. PMCID: PMC5808429. https://doi.
19. Eugène D, Djemli A, Van Vliet G. Sexual dimorphism of thyroid org/10.4158/EP171881.OR.
function in newborns with congenital hypothyroidism. J Clin 33. Mathai S, Cufield WS, Gunn AJ, et al. A novel therapeutic paradigm to
Endocrinol Metab, 2005;90(5):2696-700. PMID: 15728201. https://doi. treat congenital hypothyroidism. Clin Endocrinol (Oxf). 2008;69(1):142-
org/10.1210/jc.2004-2320. 7. PMID: 18598275. https://doi.org/10.1111/j.1365-2265.2008.03172.x.
20. Hofman P. Insights into the diagnosis and management of congenital 34. Léger J, Olivieri A, Donaldson M, et al. European Society for Paediatric
hypothyroidism. Int J Pediatr Endocrinol. 2015;2015(Suppl 1):O18. Endocrinology consensus guidelines on screening, diagnosis, and
PMCID: PMC4428806. https://doi.org/10.1186/1687-9856-2015-S1-O18. management of congenital hypothyroidism. J Clin Endocrinol Metab.
21. Rosenthal M, Addison GM, Price DA. Congenital hypothyroidism: 2014;99(2):363-84. PMID: 24446653. PMCID: PMC4207909. https://
Increased incidence in Asian families. Arch Dis Child. 1988;63(7): doi.org/10.1210/jc.2013-1891.
790-3. PMID: 3415295. PMCID: PMC1779081. https://doi.org/10.1136/
adc.63.7.790.
22. Grant D, Smith I. Survey of neonatal screening for primary
hypothyroidism in England, Wales, and Northern Ireland 1982-4.
Br Med J (Clin Res Ed). 1988;296(6633):1355-8. PMID: 3134984.
PMCID: PMC2545827. https://doi.org/10.1136/bmj.296.6633.1355.

Authors are required to accomplish, sign and submit scanned copies of the JAFES Author Form consisting of: (1) Authorship Certification, that authors contributed
substantially to the work, that the manuscript has been read and approved by all authors, and that the requirements for authorship have been met by each author;
(2) the Author Declaration, that the article represents original material that is not being considered for publication or has not been published or accepted for
publication elsewhere, that the article does not infringe or violate any copyrights or intellectual property rights, and that no references have been made to predatory/
suspected predatory journals; (3) the Author Contribution Disclosure, which lists the specific contributions of authors; and (4) the Author Publishing Agreement
which retains author copyright, grants publishing and distribution rights to JAFES, and allows JAFES to apply and enforce an Attribution-Non-Commercial
Creative Commons user license. Authors are also required to accomplish, sign, and submit the signed ICMJE form for Disclosure of Potential Conflicts of Interest.
For original articles, authors are required to submit a scanned copy of the Ethics Review Approval of their research as well as registration in trial registries as
appropriate. For manuscripts reporting data from studies involving animals, authors are required to submit a scanned copy of the Institutional Animal Care and
Use Committee approval. For Case Reports or Series, and Images in Endocrinology, consent forms, are required for the publication of information about patients;
otherwise, appropriate ethical clearance has been obtained from the institutional review board. Articles and any other material published in the JAFES represent
the work of the author(s) and should not be construed to reflect the opinions of the Editors or the Publisher.

Vol. 35 No. 1 May 2020 www.asean-endocrinejournal.org